Bacterial resistance to antibiotics emerged shortly after the beginning of antibiotics use and has raised continuously since, but the magnitude of the problem was somehow hidden until the early nineties because of the continuous discovery and release of new antibacterial agents. Nowadays, however, we face a major global public health crisis because the pharmaceutical industry is short of new antibacterial agents. Global use of those available is still increasing and, as a consequence, the incidence of resistant bacteria in humans is reaching an alarming level worldwide.
Although bacterial resistance can emerge by direct selection of resistant pathogens at the site of infection, the increased resistance of bacterial pathogens is in most instances a two step process, in which resistance occurs first in commensal flora and is followed by horizontal transfer of resistance to pathogenic species.
However hidden, increased resistance in commensal intestinal flora is a quasi constant secondary effect of all antibiotic uses. Researchers have shown that orogastric administration of beta-lactamases in mice reduced beta-lactamase associated alterations of the indigenous microflora and overgrowth of pathogens. Transposition of this principle to humans to reduce emergence of intestinal resistance during antibiotic treatments requires the specific delivery of antibiotic-hydrolyzing enzymes to the colon. An example of this approach is described in PCT WO 2004/016248, filed on Aug. 6, 2003, the contents of which are hereby incorporated by reference in their entirety. However, there are still a large number of antibiotics which induce bacterial resistance, but can not be removed by specific enzymes. Further, many bacteria produce toxins, which cause side effects such as diarrhea when the toxins reach the colon.
Adsorbents are known to adsorb a variety of organic chemicals, such as antibiotics. However, the administration of adsorbents is typically counter-indicated with prescription of antibiotics, because the adsorbents can adsorb and therefore inactivate a large quantity of these antibiotics before they can reach the blood flow [References 3-5].
It is therefore an object of the present invention to provide a system that targets inactivating agents to the colon, using site-specific particulate delivery systems, as well as methods of inactivating antibiotics and other active agents, and methods for adsorbing deleterious or dangerous products such as, but not limited to, toxins, chemicals, allergens etc. It is a further object of the present invention to provide such a system, where the system specifically releases its content into the colon, and does not interfere with the normal site of absorption of an antibiotic, i.e. the upper gastrointestinal (“GI”) tract. The present invention provides such systems and methods.